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 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 9 year-old boy with MELAS. High dosed oral thiamine administration and high fat diet induced remarkable neurological and biochemical improvement. His mother had episodic headaches and hemiplegia, probably MELAS. He complained muscle weakness and repeated episodes of vomiting started from 2 years of age. High levels of serum lactate and pyruvate were recognized, but with no metabolic acidosis. He developed generalized muscle weakness, growth retardation, generalized convulsions and stroke-like episodes at 5 years old. Optic nerve atrophy and mental retardation gradually appeared. A muscle biopsy at 5 years old revealed numerous ragged-red fibers with excess accumulation of lipid droplets and glycogen particles. Scattered fibers had no cytochrome c oxidase (CCO) activity representing focal CCO deficiency. An electron microscopy showed markedly increased number of giant mitochondria filled with markedly proliferated complicated cristae. Pyruvate dehydrogenase complex level in the fibroblasts was within normal ranges. Serum carnitine level was normal. With oral administration of thiamine hydrochloride (1000 mg) and high fat diet (60-70%), muscle weakness improved, and lactate and pyruvate levels in the serum reduced to normal ranges, whereas the mental deterioration, muscle atrophy, pes cavus progressed very slowly. He died from cardiac and renal failures at 9 years old. Autopsied muscles showed a marked decrease in cytochrome c oxidase activity (biochemically 12.8% of the normal level), and almost all muscle fibers had no cytochrome c oxidase activity histochemically. The progression of the MELAS was probably in parallel with the decrease in CCO activity.
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PMID:[A case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) with progressive cytochrome c oxidase deficiency]. 255 13

Increasingly numerous studies are being devoted to mitochondrial diseases, notably those which involve the neuromuscular system. Our knowledge and understanding of these diseases is progressing rapidly. We owe to Luft et al. (1962) the first description of this type of diseases. Their patient, a woman, presented with clinical symptoms suggestive of mitochondrial dysfunction, major histological abnormalities of skeletal muscle mitochondria and defective oxidative phosphorylation coupling clearly demonstrated in mitochondria isolated from muscle. This clinical, histological and biochemical triad led to the definition of mitochondrial myopathies. Subsequently, the triad was seldom encountered, and most mitochondrial myopathies were primarily defined by the presence of morphological abnormalities of muscle mitochondria. This review deals with the morphological, clinical, biochemical and genetic aspects of mitochondrial encephalomyopathies. The various morphological abnormalities of mitochondria are described. These are not specific of any particular disease. They may be present in some non-mitochondrial diseases and may be lacking in diseases due to specific defects of mitochondrial enzymes (e.g. carnitine palmityl-transferase or pyruvate dehydrogenase). The clinical classification of mitochondrial encephalomyopathies is discussed. There are two main schools of thought: the "lumpers" do not recognize specific syndromes within the spectrum of mitochondrial "cytopathies", the "splitters" try to identify specific syndromes while recognizing the existence of borderline cases. The following syndromes are described: chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), MERRF syndrome (myoclonic epilepsy with ragged-red fibers), MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and Leigh and Alpers syndromes. The biochemical classification comprises five types of abnormalities: defects of transport through the mitochondrial membrane, of substrate utilization, of Krebs' cycle, of oxidative phosphorylation and of various complexes of the respiratory chain. The clinical pictures corresponding to these defects are briefly described. The genetic aspects of these diseases are especially interesting because mitochondria have their own genome coding for thirteen proteins, all of them belonging to the respiratory chain. Genetic mitochondrial diseases may result from alterations of the nuclear genome, which are transmitted by mendelian inheritance, but they may also be due to alterations of the mitochondrial genome and transmitted by non-mandelian "maternal" heredity. A few examples are discussed, including Leber's optic atrophy and MERRF syndrome. (ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mitochondrial encephalomyopathies. 268 27

A 12-year-old boy with corticosteroid-responsive mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is described. His mother proved to have an asymptomatic mitochondrial myopathy on examination of a muscle biopsy specimen. Three weeks after the onset of vomiting, headache, ataxia and visual and speech impairment, he presented with a background of somatic growth retardation, deafness and school failure. Examination revealed disorientation, dysphasia, dyspraxia, optic atrophy, hemianopia, hemiparesis and sensory inattention. A cranial computed tomographic scan disclosed a large, low-density area, which was consistent with infarction, in the left posterior hemisphere and marked calcification of the basal ganglia bilaterally. Within two weeks of the commencement of corticosteroid treatment, the neurological dysfunction resolved. Attempts to decrease the dosage of dexamethasone caused an exacerbation of symptoms repeatedly. Two weeks after ceasing corticosteroid therapy, the patient developed a serious neurological relapse and a new, large, low-density area, which resembled an infarction, in the right posterior hemisphere on a computed tomographic scan. The reintroduction of corticosteroid therapy again resulted in the rapid resolution of all symptoms. It became evident that the patient had an exquisitely sensitive corticosteroid dependency, whereby a reduction in the dexamethasone dosage of even 0.25 mg a day caused confusion, headaches and increasing lactic acidaemia. Although it is difficult to assess the impact of various therapies in MELAS because of the episodic natural course of the disease, this remarkable corticosteroid responsiveness also has been noted in four previously reported patients with MELAS syndrome; therefore, it would seem reasonable to suggest that corticosteroid therapy now should be considered as standard treatment for this condition. However, corticosteroid therapy in other forms of mitochondrial disorders still awaits careful evaluation.
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PMID:Mitochondrial encephalomyopathy with corticosteroid dependence. 273 98

The case of 12 years-old boy with seizures, headache, severe vomit and focal neurological signs is reported. These episodes had several recurrences and regression with little neurologic deficits. In the investigation it was found: lactic acidosis; stroke like episodes and calcification in the basal ganglia on computerized axial tomography; ragged red fibers on muscle biopsy and decreased of cytochrome C oxidase in the muscle tissue. A revision about mitochondrial disorders with involvement of the central nervous system and muscle is made, with emphasis on diagnosis and recognition of MELAS.
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PMID:[MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes): report of a case]. 283 Aug 68

Identical twins developed myoclonic epilepsy in their teens. One twin remained mildly affected but the other went on to develop sensorineural deafness and ataxia with lactic acidosis and ragged red fibres leading to a diagnosis of mitochondrial encephalopathy. Multiple stroke-like episodes with hemiparesis followed, indicating progression from a MERRF to a MELAS phenotype. Biochemical studies revealed a severe deficiency of mitochondrial NADH-ubiquinone reductase and a moderate deficiency of cytochrome aa3. Western immunoblotting experiments using polyclonal antibodies raised against human placental cytochrome oxidase identified a similar profile of bands to those seen in controls, supporting the view that cytochrome aa3 deficiency in this case may be a secondary consequence of a failure of assembly related to a severe proximal respiratory chain defect.
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PMID:Progression from MERRF to MELAS phenotype in a patient with combined respiratory complex I and IV deficiencies. 285 17

Two patients with visual agnosia underwent visual recognition and neuropsychological tests to characterize their perceptual functioning. Both had an initial "apperceptive profile" and evolved from cortical blindness. One had carbon monoxide intoxication and incidental agenesis of the splenium of the corpus callosum; the other had the clinical features of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome). The agnosia profile showed impaired object recognition but adequate visual matching and copying of unrecognized items. The patients were successful on form discrimination, mental rotation, and visuospatial skills, but did poorly on figure-ground discrimination, visual integration, facial discrimination, and constructional tasks. Their performances were characterized by slow, serial analysis of visual features and a decreased useful field of view. The pattern of results suggests a form of visual agnosia caused by disturbances of parallel distributed processing.
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PMID:Visuoperceptual function in visual agnosia. 318 10

This is a case report on a patient with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). This study documents, by CT scan, the progression of the disease for 7 years. The first CT scan was normal; all subsequent CT scans were pathological. In addition, one MRI study was done.
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PMID:[The MELAS syndrome. Computed tomographic documentation of its course and magnetic resonance tomography]. 319 17

Two patients are reported with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes in whom CT documented massive focal brain swelling with midline shift concurrent with exacerbations of their conditions. Brain swelling producing mass effect should be recognized as a feature of MELAS.
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PMID:Massive focal brain swelling as a feature of MELAS. 324 75

Severe prolonged migrainous symptoms and prolonged partial status epilepticus are characteristic features of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Maternal transmission previously found in myoclonus epilepsy and ragged-red fibers (MERRF), another mitochondrial disease, is suggested in this disorder as well.
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PMID:MELAS syndrome: characteristic migrainous and epileptic features and maternal transmission. 336 73

MELAS is a distinctive syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis, and recurrent stroke-like episodes such as seizures, alternating hemiparesis, hemianopsia, or cortical blindness. Pathologically the disorder is characterized by multiple, solitary or continuous foci of necrosis (infarct or softening), varying in size and stage, predominantly involving the bilateral cerebral cortices and to a lesser degree cerebral white matter, basal ganglia, brainstem and cereblum. The distribution of the lesions does not correspond to vascular territories, suggesting that they are not due to usual thrombotic or embolic process. The exact nature and pathogenesis of these lesions with characteristic distribution pattern remain to be elucidated. We studied systematically cerebral blood vessels from two autopsied patients with MELAS by electron microscopy. All the main cerebral arteries including anterior, middle and posterior cerebral, basilar and vertebral arteries were examined at their proximal portions at the cerebral base and at their peripheral portions at the cortical surface as well as within brain parenchyma. We found marked accumulation of mitochondria in the cell bodies of smooth muscle cells and endothelial cells and numerous smooth muscle cells showing degeneration or necrosis, sporadically or in clusters in the tunica media. These abnormalities were most prominent in the walls of pial arterioles and small arteries up to 250 mu in diameter, and less frequent and severe in the larger pial arteries and intracerebral arterioles and small arteries. These vascular changes are different from any of those described in various disorders known to involve the cerebral blood vessels and are thus characteristic to the cerebral blood vessels of MELAS. We think that these peculiar vascular changes called mitochondrial angiopathy are caused by primary mitochondrial dysfunction in the vascular smooth muscle cells and endothelial cells themselves, as is the same in the skeletal and cardiac muscles in this disease, and that they constitute the pathogenic base of the brain lesions with unusual distribution pattern and nature in MELAS.
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PMID:[Mitochondrial angiopathy in the cerebral blood vessels of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes)]. 337 Jan 63


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